Local control of experimental malignant pancreatic tumors by treatment with a combination of chemotherapy and intratumoral 224Radium-loaded wires releasing alpha-emitting atoms

Ablation of experimental colon cancer by intratumoral224Radium-loaded wires is mediated by alpha particles released from atoms which spread in the tumor and can be augmented by chemotherapy

“…Treatment with two 224 Ra-loaded wires and 5-FU had a pronounced retardation eff ect that further led to complete cure of 4 out of 5 mice. DaRT treatment could also be eff ectively combined with chemotherapy to treat squamous cell (Cooks et al 2009b) and pancreatic carcinoma (Horev-Drori et al 2012). Yet, exposure of tumor cells in vitro to chemotherapeutic drugs did not increase their sensitivity to alpha particles (unpublished results), so we assume that the increase in survival of the animals treated by the combination is due to eradication of lung metastases by the chemotherapy.…”

“…In order to embed the accumulated radium ions into the wire ' s surface and thus prevent them from being removed once inside the tissue, the wire was heated in N 2 atmosphere to about 500 ° C to induce diff usion of radium from the surface to a depth of 1 -20 nanometers, which still allows considerable recoil of the alpha emitting daughters into the tumor. Th e 224 Ra activity and release rate of 220 Rn of 224 Ra-loaded wires were then characterized by an alpha particle detector (Cooks et al 2008, Horev-Drori et al 2012. Th e wires were inserted into the tumors a short time after their preparation.…”

The Radiochemical and Radiopharmaceutical Applications of Radium

“…Additionally, a significant increase in the survival rate was noted for DaRT treated mice (63% for treated vs. 29% untreated). Additional studies have shown the prospect of this therapy for treating squamous cell carcinomas [81], glioblastomas [81], melanoma [81], breast [80], colon [80,81,85], pancreatic [84], prostate [81], and lung cancers [83]. This method does have its drawbacks though.…”

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

“…These studies were mostly intended to establish the safety and efficacy of locoregional therapies and investigate whether higher drug concentration could increase efficiency and decrease or prevent systematic adverse effects. Intratumoral drug administration was also investigated as a method to sensitize the tumor to radiotherapy and systematic chemotherapy 30. Nearly 30% of newly diagnosed patients with lung cancer will develop respiratory distress, bleeding, atelectasis, and post-obstructive pneumonia due to partial or complete airway obstruction 31.…”

“…Nearly 30% of newly diagnosed patients with lung cancer will develop respiratory distress, bleeding, atelectasis, and post-obstructive pneumonia due to partial or complete airway obstruction 31. The tumor core consists of chemotherapy resistant tumor cells and intratumoral chemotherapy has been observed to sensitize these cells by delivering selected drugs into different parts of the core with radioactive coils and other agents for brachytherapy 30,32–34. In particular, it was observed that nanocarriers for chemotherapy drugs lead to improved drug diffusion and sustain release.…”